There is increasing data which suggets that a major difference between normal and malignant cells can be found in the structure and behavior of the plasma membrane. A number of these differences can be assigned to glycoprotein metabolism at the cell surface. In general, transformed cells appear to have a considerably higher rate of turnover of glycopeptides and an increased synthesis of glycoprotein. D-glucosamine and 2-deoxy-D-glucose have been shown to exert their antitumor effects by inhibiting glycoprotein synthesis. In the present study new nucleoside diphosphate sugar analogs will be prepared in which the natural pyrophosphate moiety will be replaced by methylene diphosphonate, imidodiphosphate and hypophosphate to give UDP-Glucose, UDP-Galactose, ADP-Glucose and GDP-Mannose analogs. Analogs will also be prepared in which the natural sugar and/or the heterocyclic base will be varied in addition to the pyrophosphate moiety in the hope of obtaining nucleoside phosphonate and imidophosphate sugars which will exert specific enzyme inhibition. These nucleotides will be studied as specific inhibitors of tumor glycosyltransferases. Increased permeability of the tumor cell plasma membrane results in a higher concentration of glycosyltransferases covalently attached to the outside of the tumor cell. These synthetic nucleotides should not enter normal cells and will be expected to exert inhibition as potential substrate analogs of tumors specific glycosyltransferases bound to the surface of the tumor cell. This specificity should result in antitumor agents which should be less toxic than currently employed agents. Tumor glycosyltransferases are believed to be involved in the biochemistry of metastasis. Inhibition of these enzymes could prevent tumor metastasis. These new nucleotides will be evaluated in various in vitro and in vivo tumor systems by Dr. Bernacki of Roswell Park Memorial Institute for Cancer Research, Buffalo, New York. They will also be evaluated as inhibitors of metastasis in vitro and in vivo against the Lewis Lung carcinoma model system at Roswell Park.